The spliceosome component Usp39 controls B cell development by regulating immunoglobulin gene rearrangement.
Cell Rep
; 38(6): 110338, 2022 02 08.
Article
in En
| MEDLINE
| ID: mdl-35139388
ABSTRACT
The spliceosome is a large ribonucleoprotein complex responsible for pre-mRNA splicing and genome stability maintenance. Disruption of the spliceosome activity may lead to developmental disorders and tumorigenesis. However, the physiological role that the spliceosome plays in B cell development and function is still poorly defined. Here, we demonstrate that ubiquitin-specific peptidase 39 (Usp39), a spliceosome component of the U4/U6.U5 tri-snRNP complex, is essential for B cell development. Ablation of Usp39 in B cell lineage blocks pre-pro-B to pro-B cell transition in the bone marrow, leading to a profound reduction of mature B cells in the periphery. We show that Usp39 specifically regulates immunoglobulin gene rearrangement in a spliceosome-dependent manner, which involves modulating chromatin interactions at the Igh locus. Moreover, our results indicate that Usp39 deletion reduces the pre-malignant B cells in Eµ-Myc transgenic mice and significantly improves their survival.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genes, Immunoglobulin
/
RNA Precursors
/
B-Lymphocytes
/
Spliceosomes
/
Ubiquitin-Specific Proteases
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2022
Document type:
Article
Affiliation country:
China